Radiobiological considerations in the design of fractionation strategies for intensity-modulated radiation therapy of head and neck cancers
Radiobiological considerations in the design of fractionation strategies for intensity-modulated radiation therapy of head and neck cancers
复制标题
DOI：
10.1016/s0360-3016(99)00438-1
复制
发表时间：
2000-02-01
影响因子：
7
通讯作者：
Schmidt-Ullrich, R
中科院分区：
文献类型：
--
作者：
Mohan, R;Wu, QW;Schmidt-Ullrich, R
目的：调强放射治疗（IMRT）计划的剂量分布，如果能同时对原发病给予高剂量和对亚临床病或选择性治疗区域给予低剂量，则在高适形性方面具有明显的上级优势。我们使用术语“同时整合加强”（SIB）来定义这种治疗。本文的目的是发展合适的分割策略的放射生物学原则的基础上的临床试验和常规使用的调强放射治疗头颈部（HN）癌症。分次策略旨在允许肿瘤剂量的升级，同时充分保留靶体积外的正常组织，并考虑嵌入主要靶体积内的正常组织的耐受性。方法和材料：IMRT分次方案是根据“归一化总剂量”（NTD）来指定的，即，生物等效剂量2戈伊/次。应用线性二次等效应公式将NTD转换为“标称”处方剂量。标称处方剂量的高剂量的原发性疾病，中等剂量的区域微观疾病，和较低的剂量选择性治疗的节点用于优化调强放射治疗计划。由此产生的名义剂量分布被转换回NTD分布，用于评估治疗计划。还对关键正常组织进行了类似的计算。开发的方法应用于几种HN治疗方案的相互比较，包括目前和过去使用的常规方案，以及SIE策略，这是通过比较大体肿瘤和区域疾病的生物等效NTD值以及大体肿瘤体积中嵌入的骨、肌肉和粘膜来完成的。（1）HN示例示意图用于证明SIB IMRT的剂量分布与IMRT分为大野阶段和增强阶段时的剂量分布相比更适形，与使用常规射束进行大野阶段，然后进行增强阶段的IMRT获得的剂量分布相比，两者均显示出显著的上级，（2）HN肿瘤的NTD与标称剂量的关系对肿瘤克隆原倍增时间的选择非常敏感，而对其他参数相对不敏感。(3)对于嵌入肿瘤体积中并假设接受与肿瘤相同剂量的晚期效应正常组织，SIE IMRT的生物等效NTD可能显著更高。(4)目标体积外的正常组织接收较低的剂量，由于更高的适形性的IMRT计划，生物等效的NTDs甚至更低，由于每分数在SIE strategy.Conclusions的剂量较低：IMRT剂量分布是最适形时，被设计为作为SIE交付。使用等效应放射生物学关系和已发布的HN数据，可以设计分次策略，其中适当调整原发性、局部疾病和选择性治疗体积的标称剂量水平，每个接受不同的剂量/fx，治疗体积之外的正常组织在此类策略中的风险降低，因为它们接受较低的总剂量以及较低的剂量/fx。然而，包埋在主要靶体积内并假设接受与主要靶体积相同剂量的组织的迟发效应毒性可能会造成问题。建议的分级策略的有效性和安全性需要通过仔细的临床试验进行评估，（C）2000 Elsevier Science Inc.
Purpose: The dose distributions of intensity-modulated radiotherapy (IMRT) treatment plans can be shown to be significantly superior in terms of higher conformality if designed to simultaneously deliver high dose to the primary disease and lower dose to the subclinical disease or electively treated regions. We use the term "simultaneous integrated boost" (SIB) to define such a treatment. The purpose of this paper is to develop suitable fractionation strategies based on radiobiological principles for clinical trials and routine use of IMRT of head and neck (HN) cancers. The fractionation strategies are intended to allow escalation of tumor dose while adequately sparing normal tissues outside the target volume and considering the tolerances of normal tissues embedded within the primary target volume.Methods and Materials: IMRT fractionation regimens are specified in terms of "normalized total dose" (NTD), i.e.,the biologically equivalent dose given in 2 Gy/fx. A linear-quadratic isoeffect formula is applied to convert NTDs into "nominal" prescription doses. Nominal prescription doses for a high dose to the primary disease, an intermediate dose to regional microscopic disease, and lower dose to electively treated nodes are used for optimizing IMRT plans. The resulting nominal dose distributions are converted back into NTD distributions for the evaluation of treatment plans. Similar calculations for critical normal tissues are also performed. Methods developed were applied for the intercomparison of several HN treatment regimens, including conventional regimens used currently and in the past, as well as SIE strategies, This was accomplished by comparing the biologically equivalent NTD values for the gross tumor and regional disease, and bone, muscle, and mucosa embedded in the gross tumor volume.Results: (1) A schematic HN example was used to demonstrate that dose distributions for SIB IMRT are more conformal compared to dose distributions when IMRT is divided into a large-field phase and a boost phase, Both were shown to be significantly superior compared to dose distributions obtained using conventional beams for the large-field phase followed by IMRT for the boost phase, (2) The relationship between NTD and nominal dose for HN tumors was found to be quite sensitive to the choice of tumor clonogen doubling time but relatively insensitive to other parameters. (3) For late effect normal tissues embedded in the tumor volume and assumed to receive the same dose as the tumor, the biologically equivalent NTD for the SIE IMRT may be significantly higher. (4) Normal tissues outside the target volume receive lower dose due to the higher conformality of the IMRT plans, The biologically equivalent NTDs are even lower due to the lower dose per fraction in the SIE strategy.Conclusions: IMRT dose distributions are most conformal when designed to be delivered as SIE. Using isoeffect radiobiological relationships and published HN data, fractionation strategies can be designed in which the nominal dose levels to the primary, regional disease and electively treated volumes are appropriately adjusted, each receiving different dose/fx, Normal tissues outside the treated volumes are at reduced risk in such strategies since they receive lower total dose as well as lower dose/fx. However, the late effect toxicities of tissues embedded within the primary target volume and assumed to receive the same dose as the primary may pose a problem. The efficacy and safety of the proposed fractionation strategies mill need to be evaluated with careful clinical trials, (C) 2000 Elsevier Science Inc.